Kim Natalie, Burden Steven J
Molecular Neurobiology Program, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, NY 10016, USA.
Nat Neurosci. 2008 Jan;11(1):19-27. doi: 10.1038/nn2026. Epub 2007 Dec 16.
Motor axons approach muscles that are regionally prespecialized, as acetylcholine receptors are clustered in the central region of muscle before and independently of innervation. This muscle prepattern requires MuSK, a receptor tyrosine kinase that is essential for synapse formation. It is not known how muscle prepatterning is established, and whether motor axons recognize this prepattern. Here we show that expression of Musk is prepatterned in muscle and that early Musk expression in developing myotubes is sufficient to establish muscle prepatterning. We further show that ectopic Musk expression promotes ectopic synapse formation, indicating that muscle prepatterning normally has an instructive role in directing where synapses will form. In addition, ectopic Musk expression stimulates synapse formation in the absence of Agrin and rescues the lethality of Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in particular, has a potent role in regulating the formation of synapses.
运动轴突接近区域预先特化的肌肉，因为乙酰胆碱受体在神经支配之前且独立于神经支配就聚集在肌肉的中央区域。这种肌肉预模式需要MuSK，一种对突触形成至关重要的受体酪氨酸激酶。目前尚不清楚肌肉预模式是如何建立的，以及运动轴突是否识别这种预模式。在这里，我们表明Musk的表达在肌肉中是预先模式化的，并且在发育中的肌管中早期的Musk表达足以建立肌肉预模式。我们进一步表明，异位Musk表达促进异位突触形成，这表明肌肉预模式通常在指导突触形成位置方面具有指导作用。此外，异位Musk表达在没有聚集蛋白的情况下刺激突触形成，并挽救Agrn突变小鼠的致死性，这表明突触后细胞，特别是MuSK，在调节突触形成中具有重要作用。
